Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses

Context Previous studies indicate that compound Danshen Dripping Pill (CDDP) improves the adaptation to high-altitude exposure. However, its mechanism of action is not clear. Objective To explore the protective effect of CDDP on hypobaric hypoxia (HH) and its possible mechanism. Materials and method...

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Autores principales:	Yunhui Hu, Jia Sun, Tongxing Wang, Hairong Wang, Chunlai Zhao, Wenjia Wang, Kaijing Yan, Xijun Yan, He Sun
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	hypobaric hypoxia traditional chinese medicine nf-κb nrf2 inflammation Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ede68e5ad069418bbaf12afce067359c
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spelling	oai:doaj.org-article:ede68e5ad069418bbaf12afce067359c2021-11-26T11:19:47ZCompound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses1388-02091744-511610.1080/13880209.2021.1998139https://doaj.org/article/ede68e5ad069418bbaf12afce067359c2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.1998139https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context Previous studies indicate that compound Danshen Dripping Pill (CDDP) improves the adaptation to high-altitude exposure. However, its mechanism of action is not clear. Objective To explore the protective effect of CDDP on hypobaric hypoxia (HH) and its possible mechanism. Materials and methods A meta-analysis of 1051 human volunteers was performed to evaluate the effectiveness of CDDP at high altitudes. Male Sprague-Dawley rats were randomized into 5 groups (n = 6): control at normal pressure, model, CDDP-170 mg/kg, CDDP-340 mg/kg and acetazolamide groups. HH was simulated at an altitude of 5500 m for 24 h. Animal blood was collected for arterial blood-gas analysis and cytokines detection and their organs were harvested for pathological examination. Expression levels of AQP1, NF-κB and Nrf2 were determined by immunohistochemical staining. Results The meta-analysis data indicated that the ratio between the combined RR of the total effective rate and the 95% CI was 0.23 (0.06, 0.91), the SMD and 95% CI of SO2 was 0.37 (0.12, 0.62). Pre-treatment of CDDP protected rats from HH-induced pulmonary edoema and heart injury, left-shifted oxygen-dissociation curve and decreased P50 (30.25 ± 3.72 vs. 37.23 ± 4.30). Mechanistically, CDDP alleviated HH-reinforced ROS by improving SOD and GPX1 while inhibiting pro-inflammatory cytokines and NF-κB expression. CDDP also decreased HH-evoked D-dimer, erythrocyte aggregation and blood hemorheology, promoting AQP1 and Nrf2 expression. Discussion and conclusions Pre-treatment with CDDP could prevent HH-induced tissue damage, oxidative stress and inflammatory response. Suppressed NF-κB and up-regulated Nrf2 might play significant roles in the mechanism of CDDP.Yunhui HuJia SunTongxing WangHairong WangChunlai ZhaoWenjia WangKaijing YanXijun YanHe SunTaylor & Francis Grouparticlehypobaric hypoxiatraditional chinese medicinenf-κbnrf2inflammationTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1585-1593 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypobaric hypoxia traditional chinese medicine nf-κb nrf2 inflammation Therapeutics. Pharmacology RM1-950
spellingShingle	hypobaric hypoxia traditional chinese medicine nf-κb nrf2 inflammation Therapeutics. Pharmacology RM1-950 Yunhui Hu Jia Sun Tongxing Wang Hairong Wang Chunlai Zhao Wenjia Wang Kaijing Yan Xijun Yan He Sun Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses
description	Context Previous studies indicate that compound Danshen Dripping Pill (CDDP) improves the adaptation to high-altitude exposure. However, its mechanism of action is not clear. Objective To explore the protective effect of CDDP on hypobaric hypoxia (HH) and its possible mechanism. Materials and methods A meta-analysis of 1051 human volunteers was performed to evaluate the effectiveness of CDDP at high altitudes. Male Sprague-Dawley rats were randomized into 5 groups (n = 6): control at normal pressure, model, CDDP-170 mg/kg, CDDP-340 mg/kg and acetazolamide groups. HH was simulated at an altitude of 5500 m for 24 h. Animal blood was collected for arterial blood-gas analysis and cytokines detection and their organs were harvested for pathological examination. Expression levels of AQP1, NF-κB and Nrf2 were determined by immunohistochemical staining. Results The meta-analysis data indicated that the ratio between the combined RR of the total effective rate and the 95% CI was 0.23 (0.06, 0.91), the SMD and 95% CI of SO2 was 0.37 (0.12, 0.62). Pre-treatment of CDDP protected rats from HH-induced pulmonary edoema and heart injury, left-shifted oxygen-dissociation curve and decreased P50 (30.25 ± 3.72 vs. 37.23 ± 4.30). Mechanistically, CDDP alleviated HH-reinforced ROS by improving SOD and GPX1 while inhibiting pro-inflammatory cytokines and NF-κB expression. CDDP also decreased HH-evoked D-dimer, erythrocyte aggregation and blood hemorheology, promoting AQP1 and Nrf2 expression. Discussion and conclusions Pre-treatment with CDDP could prevent HH-induced tissue damage, oxidative stress and inflammatory response. Suppressed NF-κB and up-regulated Nrf2 might play significant roles in the mechanism of CDDP.
format	article
author	Yunhui Hu Jia Sun Tongxing Wang Hairong Wang Chunlai Zhao Wenjia Wang Kaijing Yan Xijun Yan He Sun
author_facet	Yunhui Hu Jia Sun Tongxing Wang Hairong Wang Chunlai Zhao Wenjia Wang Kaijing Yan Xijun Yan He Sun
author_sort	Yunhui Hu
title	Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses
title_short	Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses
title_full	Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses
title_fullStr	Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses
title_full_unstemmed	Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses
title_sort	compound danshen dripping pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/ede68e5ad069418bbaf12afce067359c
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Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses

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